Raman spectroscopic detection of the T-Hg II-T base pair and the ionic characteristics of mercury.

Developing applications for metal-mediated base pairs (metallo-base-pair) has recently become a high-priority area in nucleic acid research, and physicochemical analyses are important for designing and fine-tuning molecular devices using metallo-base-pairs. In this study, we characterized the Hg(II)-mediated T-T (T-Hg(II)-T) base pair by Raman spectroscopy, which revealed the unique physical and chemical properties of Hg(II). A characteristic Raman marker band at 1586 cm(-1) was observed and assigned to the C4=O4 stretching mode. We confirmed the assignment by the isotopic shift ((18)O-labeling at O4) and density functional theory (DFT) calculations. The unusually low wavenumber of the C4=O4 stretching suggested that the bond order of the C4=O4 bond reduced from its canonical value. This reduction of the bond order can be explained if the enolate-like structure (N3=C4-O4(-)) is involved as a resonance contributor in the thymine ring of the T-Hg(II)-T pair. This resonance includes the N-Hg(II)-bonded state (Hg(II)-N3-C4=O4) and the N-Hg(II)-dissociated state (Hg(II+) N3=C4-O4(-)), and the latter contributor reduced the bond order of N-Hg(II). Consequently, the Hg(II) nucleus in the T-Hg(II)-T pair exhibited a cationic character. Natural bond orbital (NBO) analysis supports the interpretations of the Raman experiments.

[Clinical study of enterovesical fistulas].

We conducted a retrospective review of 16 patients who were diagnosed with enterovesical fistula in our hospital between January 2000 and July 2013. The patient's median age was 74 years old and 4 were female. Most of the chief complaints were pneumaturia and fecaluria. There was a vesicosigmoidal fistula in 12 patients, an ileovesical fistula in 2, and a rectovesical fistula in 2. The main underlying cause was diverticulitis in 9 patients and a sigmoid colon carcinoma in 3. Diagnoses were made based on the findings of cystoscopy, barium enema, abdominal computed tomography and so on. Treatment varied in each case depending on the etiology and the patient's condition. The procedure was mostly open surgery, but laparoscopic sigmoidectomy was performed preserving the bladder in the two most recent cases.

Involvement of histidine residues in the pH-dependent ß-galactoside binding activity of human galectin-1.

The pH dependence of the ß-galactoside binding activity of human galectin-1 (hGal-1) was investigated by fluorescence spectroscopy using lactose as a ligand. The obtained binding constant Kb was 2.94 ± 0.10 mM(-1) at pH 7.5. The Kb value decreased at acidic pH with a midpoint of transition at pH 6.0 ± 0.1. To elucidate the molecular mechanism of the pH dependence, we investigated the structures of hGal-1 and its two His mutants (H44Q and H52Q) using fluorescence, circular dichroism, UV absorption, and UV resonance Raman spectroscopy. Analysis of the spectra has shown that the pKa values of His44 and His52 are 5.7 ± 0.2 and 6.3 ± 0.1, respectively. The protonation of His52 below pH 6.3 induces a small change in secondary structure and partly reduces the galactoside binding activity. On the other hand, the protonation of His44 below pH 5.7 exerts a cation-π interaction with Trp68 and largely diminishes the galactoside binding activity. With reference to the literature X-ray structures at pH 7.0 and 5.6, protonated His52 is proposed to move slightly away from the galactoside-binding region with a partial unfolding of the ß-strand containing His52. On the other hand, protonated His44 becomes unable to form a hydrogen bond with galactoside and additionally induces a reorientation and/or displacement of Trp68 through cation-π interaction, leading to a loosening of the galactoside-binding pocket. These structural changes associated with His protonation are likely to be the origin of the pH dependence of the galactoside binding activity of hGal-1.

Pro-oxidant copper-binding mode of the Apo form of ALS-linked SOD1 mutant H43R denatured at physiological temperature.

The mutation of Cu,Zn-superoxide dismutase (SOD1), a major antioxidant enzyme, is associated with amyotrophic lateral sclerosis (ALS). In a previous study, we showed that the metal-depleted apo form of an ALS-linked mutant, H43R, undergoes denaturation at physiological temperature (37 °C) in 90 min and acquires pro-oxidant activity in the presence of Cu(2+) and H2O2. In this study, we have examined the Cu(2+)-binding mode of denatured apo-H43R by circular dichroism (CD), fluorescent oxidation, UV Raman spectroscopy, and photooxidation. CD spectroscopy indicates that denatured apo-H43R loses native ß-barrel structure and the binding of Cu(2+) to the denatured apo form induces local refolding. Fluorescent-oxidation assays in the absence and presence of Cu(2+) chelators show that denatured apo-H43R contains two Cu(2+)-binding sites with higher and lower Cu(2+) affinities and with pro-oxidant activities in the reverse order. UV Raman spectroscopy gives evidence that His residues are bound to Cu(2+) mainly through the imidazole Nτ atom at the higher-affinity site and through the Nπ atom at the lower-affinity site, sharing one His residue with each other. The Cu(2+)-binding mode of denatured apo-H43R is analogous to but different from the Cu,Zn-binding mode of the native holo form. Photooxidation experiments confirm the involvement of His residues in the pro-oxidant activity. Taken together, it is suggested that the binding of Cu(2+) induces the local refolding of denatured apo-H43R to create toxic catalytic centers that convert the enzyme from antioxidant to pro-oxidant, leading to the pathogenesis of ALS. His residues are essential for both Cu(2+)-binding and pro-oxidant activities.

Molecular magnetism of M6 hexagon ring in D(3d) symmetric [(MCl)6(XW9O33)2](12-) (M = Cu(II) and Mn(II), X = Sb(III) and As(III)).

Ferromagnetic [n-BuNH(3)](12)[(CuCl)(6)(SbW(9)O(33))(2)]·6H(2)O (1) and antiferromagnetic [n-BuNH(3)](12)[(MnCl)(6)(AsW(9)O(33))(2)]·6H(2)O (4) have been synthesized and structurally and magnetically characterized. Two complexes are structural analogues of [n-BuNH(3)](12)[(CuCl)(6)(AsW(9)O(33))(2)]·6H(2)O (2) and [n-BuNH(3)](12)[(MnCl)(6)(SbW(9)O(33))(2)]·6H(2)O (3) with their ferromagnetic interactions, first reported by us in 2006. (1) When variable temperature (T) direct current (dc) magnetic susceptibility (χ(M)) data are analyzed with the isotropic exchange Hamiltonian for the magnetic exchange interactions, χ(M)T vs T curves fitted by a full matrix diagonalization (for 1) and by the Kambe vector coupling method/Van Vleck's approximation (for 4) yield J = +29.5 and -0.09 cm(-1) and g = 2.3 and 1.9, respectively. These J values were significantly distinguished from +61.0 and +0.14 cm(-1) for 2 and 3, respectively. The magnetization under the pulsed field (up to 10(3) T/s) at 0.5 K exhibits hysteresis loops in the adiabatic process, and the differential magnetization (dM/dB) plots against the pulsed field display peaks characteristic of resonant quantum tunneling of magnetization (QTM) at Zeeman crossed fields, indicating single-molecule magnets for 1-3. High-frequency ESR (HFESR) spectroscopy on polycrystalline samples provides g(∥) = 2.30, g(⊥) = 2.19, and D = -0.147 cm(-1) for 1 (S = 3 ground state), g(∥) = 2.29, g(⊥) = 2.20, and D = -0.145 cm(-1) for 2 (S = 3), and g(∥) = 2.03 and D = -0.007 cm(-1) for 3 (S = 15). An attempt to rationalize the magnetostructural correlation among 1-4, the structurally and magnetically modified D(3d)-symmetric M (=Cu(II) and Mn(II))(6) hexagons sandwiched by two diamagnetic α-B-[XW(9)O(33)](9-) (X = Sb(III) and As(III)) ligands through M-(µ(3)-O)-W linkages, is made. The strongest ferromagnetic coupling for the Cu(6) hexagon of 2, the structure of which approximately provides the Cu(6)(µ(3)-O)(12) cylindrical geometry, is demonstrated by the polarization mechanism based on the point-dipole approximation, which provides a decrease of the ferromagnetic interaction due to the out-of-cylinder deviation of the Cu atoms for 1. The different nature of the magnetic exchange interaction in 3 and 4 is understood by the combined effect of the out-of plane deviation (the largest for 4) of the Mn atoms from the Mn(µ(3)-O)(2)Mn least-squares plane and the antiferromagnetic contribution arising from the large Mn-O-Mn bond angle. The primary contribution to D is discussed in terms of the magnetic dipole-dipole interaction between the electrons located on the magnetic sites in the M(6) hexagon.

Structural instability and Cu-dependent pro-oxidant activity acquired by the apo form of mutant SOD1 associated with amyotrophic lateral sclerosis.

Cu,Zn-superoxide dismutase (SOD1) is a cytosolic antioxidant enzyme, and its mutation has been implicated in amyotrophic lateral sclerosis (ALS), a disease causing a progressive loss of motor neurons. Although the pathogenic mechanism of ALS remains unclear, it is hypothesized that some toxic properties acquired by mutant SOD1 play a role in the development of ALS. We have examined the structural and catalytic properties of an ALS-linked mutant of human SOD1, His43Arg (H43R), which is characterized by rapid disease progression. As revealed by circular dichroism spectroscopy, H43R assumes a stable ß-barrel structure in the Cu(2+),Zn(2+)-bound holo form, but its metal-depleted apo form is highly unstable and readily unfolds or misfolds into an irregular structure at physiological temperature. The conformational change occurs as a two-state transition from a nativelike apo form to a denatured apo form with a half-life of ∼0.5 h. At the same time as the denaturation, the apo form of H43R acquires pro-oxidant potential, which is fully expressed in the presence of Cu(2+) and H(2)O(2), as monitored with a fluorogenic probe for detecting pro-oxidant activity. Comparison of d-d absorption bands suggests that the Cu(2+) binding mode of the denatured apo form is different from that of the native holo form. The denatured apo form of H43R is likely to provide non-native Cu(2+) binding sites where the Cu(2+) ion is activated to catalyze harmful oxidation reactions. This study raises the possibility that the structural instability and the resultant Cu-dependent pro-oxidant activity of the apo form of mutant SOD1 may be one of the pathogenic mechanisms of ALS.

[Conformational regulation of amyloid beta-peptide by lipid membranes and metal ions].

Conformational transition of monomeric amyloid beta-peptide (Abeta) to a self-associated beta-sheet structure is considered to be an initial step in the development of Alzheimer's disease. Several lines of evidence suggest that physiologically abundant lipid membranes and metal ions are involved in this step. We have demonstrated that Abeta binds to the phosphatidylcholine membrane in the lamellar gel phase but not in the liquid crystalline phase by using fluorescence and circular dichroism spectroscopy. The membrane-bound Abeta molecule takes alpha-helical or beta-sheet structure depending on the temperature. Tightly packed phosphatidylcholine membranes appear to serve as a platform for non-electrostatic binding and self-association of Abeta. We have also examined Zn(II) and Cu(II) binding modes of Abeta by Raman spectroscopy. The Raman spectra demonstrate that three histidine residues in the N-terminal region of Abeta provide primary metal binding sites. Zn(II) binds to the N(tau) atom of histidine and the peptide aggregates through intermolecular His-Zn-His bridges. In contrast, Cu(II) ion is chelated by the N(pi) atom of histidine and deprotonated main-chain amide nitrogens to form a soluble complex. Our findings on the conformational regulation of Abeta may help in better understanding the molecular basis for the development of Alzheimer's disease.

Incidence of upper urinary tract stone during 15 years in Tajima area, Japan: a hospital-based study.

Time trend of incidence of upper urinary tract stone during 15 years was evaluated by hospital-based cohort study in Tajima area, northern part of Hyogo prefecture, Japan, which has only two general hospitals with Department of Urology. Due to isolation in terms of traffic network and geographic circumstances, almost all patients with urinary stone in Tajima area are referred to the two hospitals. During the period 2005-2007, patients of the two hospitals with radiologically proven upper urinary tract stone were included in this study. The survey included the age and gender, location of stones, history of urinary stone, treatment received, and stone composition, if available. Annual incidence of upper urinary tract stone was estimated using the data of population census of Japan 2005 and compared with the data of Tajima during 1991-1993. 1,305 patients were included in this study. Age-adjusted incidence (+/-95% CI) was 157 (+/-22.4) for men, and 57 (+/-12.6) for women, compared with 141 (+/-20.7) for men, and 63 (+/-13.4) for women during 1991-1993. In total, 30.7% of patients received interventional treatment including shock wave lithotripsy, endoscopic lithotripsy and open surgery, whereas 25.3% in 1991-1993. Calcium oxalate/phosphate stone was 89.6%, struvite stone was 4.5%, cystine stone was 1.0%, uric acid stone was 4.0%, and others were 1.0%. In Tajima area, incidence of upper urinary tract stone has not changed during 15 years.

Evidence for the cation-pi interaction between Cu2+ and tryptophan.

The cation-pi interaction, a noncovalent interaction of electrostatic nature between a cation and an electron-rich pi system, is increasingly recognized as an important force that influences the structures and functions of molecules including proteins. Unlike other metal cations, the transition metal cation Cu2+ is not regarded to take part in a cation-pi interaction because Cu2+ tends to oxidize the pi electron system, in particular that of Trp, and to introduce covalency in the metal-pi electron interaction. This paper reports the first spectral evidence for the cation-pi interaction between Cu2+ and Trp. The Cu2+ ion bound to the amino N-terminal Cu2+/Ni2+ binding motif composed of three amino acid residues interacts with the indole ring of the fourth Trp residue in a noncovalent manner. The Cu2+-Trp interaction produces a distinct negative band at 223 nm in circular dichroism (CD), which disappears upon mutation or depletion of the Trp residue or upon replacement of the Cu2+ ion by Ni2+. In UV absorption, a pair of negative/positive intensity changes is generated at 222/231 nm by the Cu2+-Trp interaction, being consistent with the previous observations on the indole ring interacting with K+ or a cationic His imidazole ring. The negative CD band around 223 nm is characteristic of the Cu2+-Trp pair and may be useful as a marker of the Cu2+-Trp cation-pi interaction. Coordination of negatively charged ligands to Cu2+ is suggested to be important for the cation to be involved in a cation-pi interaction.

Non-electrostatic binding and self-association of amyloid beta-peptide on the surface of tightly packed phosphatidylcholine membranes.

Self-association of amyloid beta-peptide (Abeta) is considered to be an initial step in the development of Alzheimer's disease and is known to be promoted by negatively charged lipid membranes. We have examined the possibility of non-electrostatic Abeta-membrane interaction by using neutral phosphatidylcholine lipids. Fluorescence and circular dichroism spectra have clearly shown that Abeta binds to the phosphatidylcholine membrane in the lamellar gel phase but not in the ripple gel or liquid crystalline phase, indicating the importance of the tight lipid packing characteristic of the lamellar gel phase. The Abeta-membrane binding occurs at both low and high salt concentrations, ensuring the non-electrostatic nature of the interaction. The membrane-bound Abeta molecule takes a monomeric alpha-helical or self-associated beta-sheet structure depending on the temperature, peptide/lipid ratio, and salt concentration. The flat surface of tightly packed phosphatidylcholine membranes appears to serve as a platform for non-electrostatic binding and self-association of Abeta.

[Squamous cell carcinoma of the bladder presenting with spontanenous intraperitoneal bladder rupture: a case report].

A-90-year-old woman visited complaining of nausea, vomiting, and abdominal pain. She had abdominal rigidity and signs of generalized peritonitis. On computed tomography (CT) gastrointestinal perforation was denied and irregular thickness of the bladder wall was pointed out. Cystography was performed, but bladder rupture was not confirmed. Post-cystogram-CT revealed the leakage of contrast material in the peritoneal cavity from the urinary bladder. Spontaneous intraperitoneal bladder rupture was diagnosed. Cystoscopy was performed, but no information could be obtained due to severe cloudy urine. Open laparotomy was performed. At surgery, cloudy fluid was aspirated from the abdominal cavity. Abdominal organs were normal when explored, but a small perforation was found on the vault of the bladder and primary closure was performed. Postoperatively, cystoscopy was performed again after the medication with antibiotics. A huge, nonpapillary tumor was seen on the left lateral wall. Tumor biopsy was performed. Histological examination of specimens revealed squamous cell carcinoma. On abdominal CT, invasive bladder carcinoma, left hydronephrosis and hydroureter were pointed out. Considering her age, general health status and prognosis, only right ureterocutaneostomy was performed.

[Gluteal muscular metastasis from renal pelvic tumor].

We present a case of gluteal muscular metastasis from a renal pelvic tumor. A 57-year-old man had undergone right nephroureterectomy and received 2 courses of adjuvant chemotherapy (MEC: methotrexate, epirubicin, cisplatin) for invasive renal pelvic tumor. Five months after the operation, computed tomography (CT) revealed pulmonary metastasis and right adrenal gland recurrence. He underwent 2 courses of chemotherapy (gemcitabine, paclitaxel). Postchemotherapy-CT scan showed a 2.2 cm mass in the right gluteal muscle. Since the size of the pulmonary metastasis and right adrenal gland recurrence showed no change, the gluteal mass was excised. Pathological diagnosis was metastatic urothelial carcinoma. Adjuvant chemotherapy (TIN: paclitaxel, ifosfamide, nedaplatin) 3 courses were performed, but postchemotherapy-CT scan showed a new 2.4 cm mass in the right gluteal muscle. He received radiation therapy (total 30 Gy) for the new gluteal mass. The common metastatic sites of renal pelvic tumor are lungs, liver, bone, and lymph nodes. Gluteal muscle is an uncommon site of metastasis of urothelial carcinoma. This is the 1st case of gluteal muscle metastasis from renal pelvic tumor in the literature.

[A case of angiomyolipoma in a horseshoe kidney].

The patient was 52 years old. She had undergone a breast cancer operation 4 years before this visit. On computed tomography (CT), a left renal tumor in a horseshoe kidney was incidentally pointed out. CT scan showed a 1.8-cm enhanced tumor in the upper pole of the left kidney. It was hyperechoic on ultrasonography. Since renal cell carcinoma could not be excluded preoperatively, left partial nephrectomy was performed. Pathological diagnosis was a renal angiomyolipoma. The incidence of horseshoe kidney is 1 in 400. The occurrence of hydronephrosis, infection and calculous disease is not uncommon. However, a case of angiomyolipoma simultaneously with a horseshoe kidney is very rare, this being the 7th case in the literature.

[Ureteral avulsion: a rare complication of ureteroscopy].

A case of ureteral avulsion as a complication of ureteroscopy is presented. A 55-year-old woman was admitted to the hospital with the complaint of hematuria. The intravenous pyelography revealed a calculus measuring 16 x 12 mm located in the left upper ureter. Transurethral ureterolithotripsy was performed with 8 F rigid ureteroscopy. A safety guide wire was inserted and left ureteral olifice was dilated to 9 F. The ureteroscopy was smoothly introduced just under the stone. The stone was fragmentated with a pneumatic lithotripter. A part of the stone was pushed back to the renal pelvis, so the ureteroscope was passed to that stone and fragmentation was done as much as possible. The ureteroscopy was gently pulled out to the bladder, but the distal ureter was torn at the ureteral orifice and could be seen at the urethral orifice. Pelvis, upper ureter and middle ureter were intact, so open intervention for repair was not performed. A 6Fr double pigtail stent was placed over the safety guidewire. Cystscopy indicated a part of the distal ureter was protruded from the ureteral orifice. Eight weeks later, the protruded part of ureter was necrotic and calcified for ischemia. Transurethral resection of necrotic ureter was performed. Histologically, resected ureter changed necrotic tissue for ischema. Postoperatively intravenous pyelography did not reveal left hydronephrosis and cystoscopy indicated that the left ureteral orifice was almost normally repaired.

[Renal cell carcinoma with malignant pleural mesothelioma after asbestos exposure: a case report].

A 66-year-old man visited complaining of cough and sore throat. He had been exposed to asbestos 43 years ago. Chest X-ray revealed left pleural effusion and abnormal shadow in the right lung field. Chest computed tomography (CT) showed multiple enhanced nodules in the right pleural cavity. Abdominal CT showed a 3-cm enhanced tumor in the lower pole of the left kidney. Left radical nephrectomy was performed. Pathological diagnosis was renal cell carcinoma. Postoperatively pleural biopsy was performed by using thoracoscopy. White plaque was seen at the costal pleura and surface of lung. Pathological diagnosis was malignant pleural mesothelioma based on using mesothelium-associated antibodies: calretinin (+), CK5/6 (+), D2-40 (+), HBME-1 (+), TTF-1 (-), MOC31 (-), CEA (-). Combination therapy (extrapleural pneumonectomy, chemotherapy, and radiotherapy) was initiated. Malignant mesothelioma is a devastating neoplasm with a strong etiological relationship with asbestos exposure. The incidence is rising in industrialized countries, with the peak expected in the year 2020. However, renal cell carcinoma with malignant pleural mesothelioma is very rare and this is the 2nd case in the Japanese literature.

Bead-like passage of chloride ions through ClC chloride channels.

The ClC chloride channels control the ionic composition of the cytoplasm and the volume of cells, and regulate electrical excitability. Recently, it has been proposed that prokaryotic ClC channels are H+-Cl- exchange transporter. Although X-ray and molecular dynamics (MD) studies of bacterial ClC channels have investigated the filter open-close and ion permeation mechanism of channels, details have remained unclear. We performed MD simulations of ClC channels involving H+, Na+, K+, or H3O+ in the intracellular region to elucidate the open-close mechanism, and to clarify the role of H+ ion an H+-Cl- exchange transporter. Our simulations revealed that H+ and Na+ caused channel opening and the passage of Cl- ions. Na+ induced a bead-like string of Cl- -Na+-Cl--Na+-Cl- ions to form and permeate through ClC channels to the intracellular side with the widening of the channel pathway.

[Prostate cancer detection by prostate biopsy among Japanese with prostate-specific antigen below 4.0 ng/ml].

The cases of prostate cancer diagnosed at our hospital after the introduction of transrectal ultrasound-guided prostate biopsy were analyzed to ascertain the cancer detection rate among individuals with a prostate-specific antigen (PSA) below 4.0 ng/ml and to assess the pathological characteristics of the prostatectomy specimens. During the period from January 1997 to December 2003, 1,167 individuals received prostate biopsies at our hospital. Before March 2003, the PSA cut-off level for biopsy was set at 4.0 ng/ml, but a biopsy was sometimes performed if a rectal examination revealed abnormalities or the patient desired a biopsy with a PSA below 4.0 ng/ml. After April 2003, all individuals with a PSA over 3.1 ng/ml were biopsied. The results of the prostate biopsy and the pathology data on radical prostatectomy specimens were compared between individuals with a PSA below 4.0 ng/ml and those with a PSA of 4.1-10 ng/ml. The prostate cancer detection rate among individuals with a PSA between 3.1 and 4.0 ng/ml was 19.4% (12/62) before March 2003 and 15.6% (7/45) after April 2003. The number of cancer-positive core was significantly lower among individuals with a PSA below 4.0 ng/ml. On prostatectomy specimens the percentage of surgical margin positive cases was significantly higher among individuals with a PSA below 4.0ng/ml (17 cases) than those with a PSA of 4.1-10 ng/ml (67 cases), although there was no significant difference between these two groups in terms of the pathological stage and Gleason score. Our results indicate that the prostate cancer detection rate is also high among Japanese men with a PSA below 4.0 ng/ml. The biopsy results and pathological features for prostate cancer with a PSA below 4.0 ng/ml did not differ markedly from prostate cancer with a PSA in the gray zone (4.1-10.0 ng/ml).

[Clinical review of conservative management of upper urinary tract transitional cell carcinoma].

We reviewed 18 patients with transitional cell carcinoma of the renal pelvis and ureter undergoing nephron-sparing surgery between April 1990 and Febrary 2003. The mean age of the patients, 17 males and one female, was 69 years (range 33-88 years). The tumor site was the renal pelvis in 2, ureter in 13 and ureteral orfice in 2. Six of them were imperative cases and 12 were elective. Eight patients underwent endourological treatment and 10 patients open surgery including partial ureterectomy performed on 8 patient. The follow up period was 3 to 104 months (mean 37 months). Among those defined as imperative, the histopathological stage was pT1 in one, pT2 in one, pT3 in 3 and one in pT4. Among the elective cases, the histopathological stage was pTa in 7, pT1 in 2, pT2 in one, pT3 in 2 patients. Of the three defired as elective with tumors cT2 or higher, two died of disease. The 5-year survival rate was 50% and 68% in the imperative and elective cases, respectively. In the patients with tumors pT2 or higher and/or grade 3, the prognosis was poor which suggests the need for intensive therapy including lymph node dissection and/or adjuvant chemotherapy. It is necessary to consider the possibility of selecting nephron-sparing surgery for locally advanced tumors.

Roles of the histidine and tryptophan side chains in the M2 proton channel from influenza A virus.

The M2 protein form influenza A virus forms a tetrameric ion channel, which enables proton passage across biological membranes when the N-terminal side is acidified. Among the amino acid residues in the transmembrane domain of the M2 protein, His37 and Trp41 are essential for the pH-regulated proton conductance. Current knowledge about the structures and interactions of His37 and Trp41 suggests a model for the M2 ion channel, in which the channel is closed by a network of His37 hydrogen bonds at neutral pH and is opened by a His37-Trp41 cation-pi interaction at acidic pH.